Phase-II study of toripalimab combined with neoadjuvant chemotherapy for the treatment of resectable esophageal squamous cell carcinoma.

Abstract

e16029 Background: Compared with neoadjuvant chemotherapy alone，Neoadjuvant radiochemotherapy can significantly increase pCR rate in esophageal squamous cell carcinoma and improve patient overall survival. However, the addition of radiotherapy increases the risk of adverse reactions and surgery. Neoadjuvant radiochemotherapy is currently used in < 5% of Chinese patients.The purpose of this phase II study is to assess the efficacy and safety of toripalimab combined with paclitaxel and cisplatin as neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma(clinical trial registration number: ChiCTR1900025318). Methods: Patients 18–75 years old with esophageal squamous cell carcinoma confirmed by endoscopic biopsy, assessed to be locally advanced esophageal squamous cell carcinoma (cT1–cT2, N+; cT3–cT4 a, any N), and expected to be resectable were given toripalimab (240 mg d1 + PTX 175 mg/m2 + PDD 75 mg/m2 q3w) before surgery for two treatment cycles, followed by efficacy assessment. A consultation meeting with thoracic surgeons was held to assess radical surgery for patients with resectable lesions 4–6 weeks after neoadjuvant therapy was completed. pCR and postoperative-stage statistical analysis were conducted based on postoperative pathology test results. These results were used to determine the efficacy and safety of PD-1 monoclonal antibody combined with chemotherapy as neoadjuvant therapy for locally advanced esophageal cancer. Results: By December 2020, 23 subjects were enrolled. Of the subjects, five withdrew without undergoing surgery (three subjects refused surgery and switched to radical radiochemotherapy, one subject progressed to PD after two cycles of neoadjuvant therapy and switched to palliative treatment, and one subject could not undergo surgery after neoadjuvant treatment and gave up the treatment) and 18 evaluable patients underwent surgery. The R0 resection rate was 100%, and T0–Tis 33.3% (6/18) achieved pCR. Among these patients, 61.1% (11/18) achieved T0–T1 after surgery, and 72.2% (13/18) achieved N0. Moreover, stage reduction effects were significant compared with preoperative TN staging. Common side-effects include nausea, vomiting, neutropenia, thrombocytopenia, rash, asthenia, constipation, and muscle soreness. Most adverse events were grades 1–2, and grades 3/4 adverse events include one case of grade 3 neutropenia and one case of grade 3 diarrhea (suspected immune-related colitis), which improved after symptomatic treatment. Conclusions: Toripalimab combined with the TP scheme showed preliminary efficacy and controllable safety in the treatment of resectable locally advanced esophageal squamous cell carcinoma and is worthy of further exploration. Clinical trial information: ChiCTR1900025318.

Evaluation of Clinical and Safety Outcomes of Neoadjuvant Immunotherapy Combined With Chemotherapy for Patients With Resectable Esophageal Cancer

“…The geographic distribution of included studies is shown in eFigure 1 in the Supplement. non-RCTs, and 25 of them were single-group 21,22,[24][25][26][27]30,31,[33][34][35][36][37][39][40][41][42][43][44][45][46][47] and 2 were dual-group trials. 28,29 Twenty-three trials 21,23,24,[27][28][29][31][32][33][34][35][36][37][38][39][42][43][44]46,47 enrolled patients with ESCC and applied anti-PD-1 antibody.…”

“…non-RCTs, and 25 of them were single-group 21,22,[24][25][26][27]30,31,[33][34][35][36][37][39][40][41][42][43][44][45][46][47] and 2 were dual-group trials. 28,29 Twenty-three trials 21,23,24,[27][28][29][31][32][33][34][35][36][37][38][39][42][43][44]46,47 enrolled patients with ESCC and applied anti-PD-1 antibody. Four trials 22,26,30,45 enrolled patients with EAC, of which 2 used anti-PD-1 antibody 30,45 and 2 applied anti-PD-L1 antibody.…”

“…The remaining 89 full-text articles were evaluated for eligibility, 62 of which were removed because they provided outdated preliminary results or lacked valid data. Thus, 27 prospective studies 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 were included in the final qualitative and quantitative synthesis ( Figure 1 ). The geographic distribution of included studies is shown in eFigure 1 in the Supplement .…”

“…Meanwhile, based on 17 trials, 23,25,27,30,[33][34][35][36][37][38][39][40][41][42][43]46,47 the pooled MPR rate was 48.9% (95% CI, 42.0%-55.9%), with mild heterogeneity (I 2 = 50.3%; 95% CI, 13.1%-71.5%; P = .10) (Figure 3). In terms of safety, 14 trials, 23,26,27,29,32,34,36,38,40,42,[44][45][46]48 23,[27][28][29]31,[33][34][35][37][38][39][40][41][42]44,[46][47][48] was 98.6% (95% CI, 97.1%-99.6%), with no evidence of significant heterogeneity (eFigure 9 in the Supplement).…”

Toripalimab: the First Domestic Anti-Tumor PD-1 Antibody in China

“…In a phase II study (ChiCTR1900025318), 23 subjects with resectable ESCC were included and given toripalimab combined with paclitaxel and cisplatin as neoadjuvant treatment. Among the evaluable patients, 33.3% (6/18) achieved pCR ( 59 ). The combination regime also showed a controllable safety profile, and grade 3–4 treatment-related adverse events (TRAEs) were reported in two patients.…”